A large proportion of diet-derived glucose is taken up by skeletal muscle in response to insulin, and excess glucose is stored in muscle as glycogen until mobilized. In addition, muscle burns large amounts of fat via mitochondrial β-oxidation in response to energy demands. Insulin resistance in skeletal muscle has long been recognized to be an important underlying mechanism of type 2 diabetes. While the importance of skeletal muscle in controlling whole-body glucose and lipid metabolism is well established, its role as an endocrine tissue that secretes biologically active polypeptide hormones and cytokines (collectively termed myokines) involved in modulating metabolic, inflammatory, and other physiological processes in non-muscle tissues has only recently been investigated.
Recent proteomics studies focusing on the secretome (the entire complement of secreted proteins) of cultured mouse or human myotubes have revealed a large number (˜250 in human and ˜600 in mouse) of muscle cell-derived secretory proteins with potential autocrine, paracrine, and/or endocrine functions. For example, IL-6, FGF-21, Insulin-like 6 (Insl6) follistatin-like 1 (Fstl-1; also known as TSC-36), LIF, IL-7, IL-15, and musclin are currently characterized as myokines. These myokines act locally in an autocrine/paracrine manner and/or as endocrine factors linking skeletal muscle to regulation of physiological processes in other tissues.
However, the expression of all myokines described to date is not restricted to skeletal muscle—they are generally expressed by a variety of cell types, and most are, in fact, expressed at much higher levels by non-muscle tissues. Prior to the present invention, no myokine has been discovered to be preferentially expressed by skeletal muscle.
Therefore, there still exists a need for compositions suitable for use in modulation of metabolic, inflammatory and whole-body fatty acid metabolism.